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Adolescent survivors of pediatric brain tumor (PBT) are a sparsely studied subset of childhood cancer survivors. Sustaining a PBT may complicate the development of executive functions (EFs), which play a vital role in long-term psychosocial adjustment. In this study, 48 adolescent survivors and their parents completed questionnaires assessing EF, psychological symptoms, fatigue, and adaptive functioning, and 26 survivors underwent neuropsychological assessment. Survivors reported significantly more problems with adaptive functioning than a healthy control group, and this was most strongly associated to executive dysfunction, compared to psychological symptoms and fatigue. The findings have important implications for long-term follow-ups.

Although measurement of intracranial pressure (ICP) has occasionally been utilized in children with craniosynostosis (CSS), data on parameters of pulsatile ICP in CSS are still lacking, and the role of pulsatile ICP measurements in the management of CSS is not well established. From our department’s database, we retrieved the data from children in whom the measurement of static and pulsatile ICP was a part of the diagnostic work-up in different clinical situations related to CSS. Both clinical and ICP data were retrospectively reviewed and analyzed. We identified 49 children with CSS, median age 4.4 years (range 0.2–18.9), in whom a total of 67 diagnostic ICP measurements were undertaken between 2002 and 2014. The CSS was syndromal in 23 cases. The rationale for ICP measurement was a question of indication for cranial vault expansion surgery (CVES) in 12 patients (Group 1), of its timing in 10 patients (Group 2), of suspected abnormally elevated ICP or hydrocephalus in 11 patients (Group 3), of indication for repeated CVES in 13 patients (Group 4), or shunt dysfunction in three patients (Group 5). The average mean ICP for the whole cohort was 15.1 ± 5.5 mmHg and mean wave amplitude (MWA) 5.3 ± 2.2 mmHg. There was no significant difference in ICP parameters when compared between Groups 1–5. Fundoscopy revealed papilledema in five out of 32 children (15.6%). There were significantly higher parameters of pulsatile ICP (MWA) in patients with papilledema, but no statistically significant difference in parameters of static ICP. In this cohort of pediatric patients with CSS presenting with various diagnostic challenges, we found the diagnostic measurement of static and pulsatile ICP useful in selecting the optimal treatment modality and timing of surgery. Papilledema was associated with elevated pulsatile ICP, a parameter that in previous studies has been shown to correlate with impaired intracranial compliance.

Background Long-term outcome for children who underwent surgery for brain tumors in the first 3 years of life is not well-known. Methods We performed a retrospective study on surgical morbidity, mortality rate, academic achievement, and work participation in children below 3 years of age who underwent primary tumor resection for a brain tumor in the period from 1973 to 1998. Gross motor function and activities of daily life were scored according to the Barthel Index. Long-term survivors were defined as with a survival from primary diagnosis of 20 years or more. Findings Ninety-seven consecutive children were included. No patient was lost to follow-up. Gross total resection was achieved in 67 children during the primary procedure, 25 had subtotal resections, and 5 had only partial resection. The 20-year survival figures for the 46 children with high-grade tumors was 33%, and the corresponding figures for 51 patients treated for low-grade tumors was 82%. Five of the 57 20-year-survivors died 21, 29, 30, 30, and 41 years, respectively, following primary surgery. Fifty of the 52 long-term survivors had a Barthel Index (BI) of 100, while the remaining two had a BI of 40. Twelve patients were long-term survivors after treatment for HG tumors (26%), while 40 of the 51 patients treated for LG tumors (78%) were alive. Thirty-two of the 52 long-term survivors were in full-time work and 29 of them after treatment for LG tumors. Another 10 were in part-time work, while the last 10 individuals had no working capacity. Conclusion Survival is better for patients with low-grade tumors compared with those with high-grade tumors. The functional level of long-term survivors is affected by adjuvant therapy and radiotherapy in particular. Neurosurgical intervention in itself is safe and plausible for pediatric brain tumor patients below 3 years of age. However, there should be a focus on potential late affects, and survivors should be followed by knowledgeable clinical staff for the neoplastic disease as well as for potential side effects. In this consecutive series, a 33% 20-year survival for children treated for HG tumors and 82% for patients with LG tumors was observed. The patients with LG tumors who had been treated with surgical resection without any adjuvant therapy showed a good clinical outcome as adults, and two-thirds of them were in full-time work.

Background Brain tumor surgery must balance the benefit of maximal resection against the risk of inflicting severe damage. The impact of increased resection is diagnosis-specific. However, the precise diagnosis is typically uncertain at surgery due to limitations of imaging and intraoperative histomorphological methods. Novel and accurate strategies for brain tumor classification are necessary to support personalized intraoperative neurosurgical treatment decisions. Here, we describe a fast and cost-efficient workflow for intraoperative classification of brain tumors based on DNA methylation profiles generated by low coverage nanopore sequencing and machine learning algorithms. Methods We evaluated 6 independent cohorts containing 105 patients, including 50 pediatric and 55 adult patients. Ultra-low coverage whole-genome sequencing was performed on nanopore flow cells. Data were analyzed using copy number variation and ad hoc random forest classifier for the genome-wide methylation-based classification of the tumor. Results Concordant classification was obtained between nanopore DNA methylation analysis and a full neuropathological evaluation in 93 of 105 (89%) cases. The analysis demonstrated correct diagnosis in 6/6 cases where frozen section evaluation was inconclusive. Results could be returned to the operating room at a median of 97 min (range 91-161 min). Precise classification of the tumor entity and subtype would have supported modification of the surgical strategy in 12 out of 20 patients evaluated intraoperatively. Conclusion Intraoperative nanopore sequencing combined with machine learning diagnostics was robust, sensitive, and rapid. This strategy allowed DNA methylation-based classification of the tumor to be returned to the surgeon within a timeframe that supports intraoperative decision making.

Long-term shunt dependency rates in children treated for IIH with CSF diversion have not been established. We therefore present our experience with 4 children shunted for Idiopathic Intracranial Hypertension (IIH) during the years 1988-2000 with very long-time follow-up. Two out of these patients have experienced late or very late episodes of severe shunt failure during the second or third decade after initial shunt treatment. They were all boys and may not be representative for IIH patients as a whole. Two of them appear, however, to be permanently shunt dependent, indicating that long-term shunt dependency in children treated for IIH with CSF diversion may be more common than previously expected.

Long-term results for adult patients who underwent surgery for paediatric brain tumours in the first year of life have not been reported. We performed a retrospective study on surgical morbidity, mortality rate, academic achievement and/or work participation in patients who underwent primary tumour resection for a brain tumour as infants in the period from 1973 to 1998. Gross motor function and activities of daily life were scored according to the Barthel Index. Thirty-four consecutive children were included. No patient was lost to follow-up. Twenty-two children (65%) underwent gross total resection (GTR), 10 had subtotal resections (STR) and 2 had only partial resection during primary surgery. Nine children were additionally surgically treated for hydrocephalus (HC), many of them with repeat operations for shunt malfunction during follow-up. Three children died within 30 days following GTR of highly vascular tumours. Seventeen (50%) of the infants had high-grade tumours with 1-month, 1-year and 20-year survival figures of 88, 30 and 30%. The corresponding figures for 17 patients treated for low-grade tumours were 94%, 88% and 88%, respectively. Seventeen patients (50%) are still alive as adult long-term survivors at median age of 29 years (range 20 to 43 years). Three died after 29, 30 and 41 years, respectively. At the latest follow-up, 16 out of 17 long-term survivors have a Barthel Index (BI) of 100, while the remaining one has a BI of 40. Two long-term survivors of a high-grade tumour treated 30 and 35 years ago are severely handicapped and have no working capacity. The 15 long-term survivors after treatment for a low-grade tumour are all in daily activity as students (4), in part-time work (3) or full-time work (8). A brain tumour occurring in the first year of life is a serious threat to the patient and the family, particularly in case of high-grade tumours. In our small cohort, the results from long-term survivors of high-grade tumour group are depressing and confirm the deleterious effect of radiotherapy given to infants decades ago. The infants with low-grade tumours who could be treated with surgical resection without any adjuvant therapy show a good clinical outcome as adults. For parents of these latter patients, the results are far better than feared in advance.

Background Long-term outcome after surgical treatment of supratentorial ependymoma (STE) in children has not been extensively reported. Findings We identified 26 children who underwent primary tumor resection of STE between 1953 and 2011, with at least 8 years follow-up. Ten patients (38%) had anaplastic and 16 had low grade ependymoma. Four of 15 children (26%) treated in the years 1953-1976 survived more than 5 years, but the observed 10-year survival was only 7%. One patient lived for 37 years, and second surgery for a local recurrent lesion disclosed a glioblastoma, possibly secondary to radiotherapy. In contrast, the observed 5-year survival rate for 11 children treated in the years 1992-2011 was 8/11 (73%) and observed 10- and 25-year survival rates were 70% and 66%, respectively. Eight patients were alive and tumor-free with follow-up periods of 8-27 (median 18) years, all treated after 1992. Five of these long-term survivors were 23-39 years old with full-time (n = 3) or part-time (n = 2) work. The last three patients were still children (9-12 years old): one with good function and two with major neurological deficits. The majority of patients (n = 18) received adjuvant radiotherapy and eight children no adjuvant treatment. Repeated resections for residual or recurrent tumor were necessary in 11 patients (42%), mostly due to local disease with progressive clinical symptoms. Eight patients underwent only one repeat resection, whereas three patients had two or more repeat resections within 18 years after initial surgery. Four patients were tumor-free after repeated resections at the latest follow-up, 2-13 years after last surgery. Conclusion Pediatric STE has a marked risk for local recurrence even after gross total resection and postoperative radiotherapy, but survival has increased following the introduction of modern treatment in recent years. Repeated surgery is an important part of treatment and may lead to persistent tumor control.

Background Long-term outcomes for pediatric patients treated for spinal ependymoma are unknown. Methods We performed a retrospective analysis of outcome data from 33 children and young adults (0–22 years) who were operated on for a spinal ependymoma at our institution during the last 8 decades (1938–2019). Results Nineteen patients are alive, with follow-up period up to 60 years. Twelve of them are tumor-free, and 7 are alive with disease. Fourteen patients are dead, 9 of them due to recurrent and/or progressive disease 1–56 years (median: 11 years) after the initial surgery. Four of the deceased patients were treated before 1948, 3 of them with excellent long-term survival for 62–66 years after the initial surgery. Tumor recurrence was observed in half of the patients, both local at the site of the primary tumor resection as well as widespread intraspinal presentations. Recurrences were observed within months but also occurred after up to 20 years after initial treatment. After the implementation of magnetic resonance imaging in 1987, details of recurrent disease became more easily demonstrated. Repeated resections were performed when the symptomatic spinal disease was in progress (n = 11). Furthermore, 2 patients have intracranial tumor manifestations, 1 of them underwent resection of a suprasellar tumor in 1991. Four deceased patients experienced aggressive extraspinal progressive disease requiring multiple surgeries, including pulmonary metastasis in 1 of them. Conclusions Pediatric spinal ependymomas can be treated with favorable results and functional outcome may be good even after more than half a century of follow-up. Nevertheless, unexpected and late recurrences may occur, and life-long follow-up is therefore recommended.

Objective To present long-term follow-up of a consecutive single-institutional series of patients treated for choroid plexus tumors over 8 decades. Methods From 1939 to 2020, 59 children were treated for choroid plexus tumors. Median age at diagnosis was 1.7 years. Results Gross total resection was achieved in 51 patients (86%). Ten patients (17%) underwent >1 resection. During the first 4 decades of the study (1939–1979), 14 patients with plexus papillomas were treated. Operative mortality was 50%, with 6 of the remaining 7 patients experiencing excellent survival with follow-up periods of 41–81 years. In the last 4 decades (1980–2020), 38 patients had low-grade tumors, and all were alive at the latest follow-up (range, 0.5–39 years). Observed 5-year survival in this subgroup was 100% (n = 30), as was observed 10-year survival (n = 26). One of 7 (14%) patients with atypical choroid plexus papilloma and 3 of 31 patients (10%) with choroid plexus papilloma underwent a second resection owing to recurrent tumor. At last follow-up, 47 patients (80%) were alive; 45 (96%) had a Barthel Index score of 100 and 2 had a Barthel Index score of 50. Today 25 patients are adults (20–59 years old); 17 work full-time, 4 work part-time, and 4 are unable to work. Conclusions Low-grade choroid plexus tumors can be cured with gross total resection alone, with excellent long-term survival and functionality. The vast majority of survivors live independently as adults and work full-time. Recurrences are uncommon (8.7%), appear within the first few years after primary surgery, and can be treated with repeat resections.

Although measurement of intracranial pressure (ICP) has occasionally been utilized in children with craniosynostosis (CSS), data on parameters of pulsatile ICP in CSS are still lacking, and the role of pulsatile ICP measurements in the management of CSS is not well established.From our department's database, we retrieved the data from children in whom the measurement of static and pulsatile ICP was a part of the diagnostic work-up in different clinical situations related to CSS. Both clinical and ICP data were retrospectively reviewed and analyzed.We identified 49 children with CSS, median age 4.4 years (range 0.2-18.9), in whom a total of 67 diagnostic ICP measurements were undertaken between 2002 and 2014. The CSS was syndromal in 23 cases. The rationale for ICP measurement was a question of indication for cranial vault expansion surgery (CVES) in 12 patients (Group 1), of its timing in 10 patients (Group 2), of suspected abnormally elevated ICP or hydrocephalus in 11 patients (Group 3), of indication for repeated CVES in 13 patients (Group 4), or shunt dysfunction in three patients (Group 5). The average mean ICP for the whole cohort was 15.1 ± 5.5 mmHg and mean wave amplitude (MWA) 5.3 ± 2.2 mmHg. There was no significant difference in ICP parameters when compared between Groups 1-5. Fundoscopy revealed papilledema in five out of 32 children (15.6%). There were significantly higher parameters of pulsatile ICP (MWA) in patients with papilledema, but no statistically significant difference in parameters of static ICP.In this cohort of pediatric patients with CSS presenting with various diagnostic challenges, we found the diagnostic measurement of static and pulsatile ICP useful in selecting the optimal treatment modality and timing of surgery. Papilledema was associated with elevated pulsatile ICP, a parameter that in previous studies has been shown to correlate with impaired intracranial compliance.

The aim of the study was to analyze the long-term outcome (>20 years) after treatment of posterior fossa medulloblastoma (MB) in childhood. We analyzed data from patients treated for posterior fossa MB between 1974 (introduction of the first international treatment protocol in Norway) and 1987 (when use of radiotherapy was abandoned in children under 4 years of age). Out of 47 children, 24 survived >20 years. At the time of analysis, 16 patients (median age 41 years, range 32–52) were alive (median follow-up 34 years, range 30–42), while 8 patients died 22–41 years (median 31 years) after primary treatment: one late death (after 22 years) was due to tumor recurrence whilst other 7 deaths (after 23 to 41 years) were related to the detrimental effects of the treatment (secondary tumors, stroke, severe epilepsy and depression). Observed 20- and 30-year survival rates were 51% and 44%, respectively. Despite successful treatment of MB in childhood and satisfactory tumor control during the first 20 years following primary treatment, our data indicates that even long-term survivors may die from tumor recurrence. However, the main factors causing late mortality and morbidity in long-term survivors seem to be the complications related to radiotherapy given in childhood.

Background: The birth of a child with a congenital craniofacial anomaly (CFA) can have a profound psychological impact on the family. Despite the complexity and variability in treatment for these rare conditions, few studies have been conducted into parents’ emotional responses to health-care experiences. The aim of the present study was to investigate parents’ subjective experiences of their child’s condition and treatment using an in-depth qualitative approach. Methods: Individual semistructured interviews were conducted in person or over the telephone with 48 parents of children with a range of rare CFAs. Interviews were transcribed verbatim, translated into English, and analyzed using inductive thematic analysis. Results: Participants reported physical and psychological symptoms that could be indicative of medical traumatic stress in relation to their child’s diagnosis and treatment. Participants described feelings of powerlessness and the weight of being responsible for their child’s care. Yet, participants also reported that as a result of their experiences, their perspective on life had changed and they had grown in self-confidence. Conclusions: The findings provide insight into the complex physical and psychological effects experienced by parents in response to their child’s diagnosis and medical treatment, as well as an understanding of how these experiences may also result in personal growth over time. Implementation of trauma-informed evidence-based resources should be considered in craniofacial care and future research, particularly in regard to prevention and treatment of psychological distress.

Object The object of this study was to delineate long-term results of the surgical treatment of pediatric tumors classified as ganglioglioma or gangliocytoma. Methods A cohort of consecutive patients 19 years or younger who had undergone primary resection of CNS tumors during the years 1980–2016 at a single institution were reviewed in this retrospective study of surgical morbidity, mortality, and academic achievement and/or work participation. Gross motor function and activities of daily living were scored using the Barthel Index (BI). Results Patient records for 32 consecutive children and adolescents who had undergone resection for a ganglioglioma were included in this study. Of the 32 patients, 13 were in the first decade at the first surgery, whereas 19 were in the second decade. The male/female ratio was 1.0 (16/16). No patient was lost to follow-up. The tumor was localized to the supratentorial compartment in 26 patients, to the posterior fossa in 5 patients, and to the spinal cord in 1 patient. Only two of the tumors were classified as anaplastic. Of the 30 low-grade tumors, 2 were classified as gangliocytomas, 6 were desmoplastic infantile gangliogliomas, and 22 were ordinary gangliogliomas. The aim of primary surgery was gross-total resection (GTR) and was achieved in 23 patients (71.9%). Altogether, 43 tumor resections were performed. Eight patients underwent a second resection from 1 to 10 years after primary surgery and three of these also had a third resection from 2 to 24 years after initial surgery. The reason for further resection was clinical (seizure control failure/recurrence of epilepsy or progressive neurological deficit) and/or residual tumor progression/recurrence. There was no operative mortality in this series and all 32 patients are alive with follow-up periods from 0.5 to 36 years (median 14 years). Observed 14-year survival is thus 100%. One out of two children with primary anaplastic tumor received local radiotherapy (proton) postoperatively. The other 31 patients did not have any kind of non-surgical adjuvant therapy. Twenty-one out of 26 children with supratentorial tumor had epilepsy as one of their presenting symptoms. Nineteen of these became seizure-free after initial surgery (18 of them after GTR), but 3 patients experienced recurrence of seizures within some years. Functional outcome in terms of ADL, schooling, and work participation was gratifying in most patients. Five patients have persistent hydrocephalus (HC), treated with ventriculoperitoneal (VP) shunts. Conclusion Low-grade gangliogliomas (GGs) can be surgically treated with good long-term results including seizure and tumor control as well as school and working participation.

Medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor of the central nervous system (CNS-PNET) are among the most common pediatric brain tumors. The diagnosis, treatment, and outcome of MB/CNS-PNET patients treated during the last four decades at Oslo University Hospital (OUH) are described.All patients younger than 20 years of age diagnosed and treated for MB/CNS-PNET at OUH between 1 January 1974 and 31 December 2013 were identified.We found 175 patients. In 13 of them, the diagnosis was changed upon histopathological review and in 4 patients part of the treatment was administered at other hospitals. Thus, 158 patients were included for further analysis. Eight patients did not receive adjuvant therapy because of a dismal clinical condition. The overall 5-year survival rate for MB and CNS-PNET was 54%, for MB 57%, and for CNS-PNET 41%. Gross total resection (GTR) was achieved in 118 patients and 5-year overall survival for patients with GTR versus those with non-GTR differed significantly with 64% versus 22%. Cytological examination of the cerebrospinal fluid was performed in 52 patients. A total of 126 patients received radiotherapy as part of the primary treatment and 24 did not due to young age. Median time from surgery to start of radiotherapy was 33 days. Duration of radiotherapy was more than 48 days in 22% of patients. At the time of analysis, 63 patients were alive and disease-free, one alive with disease, and 94 patients were deceased; 84 of these due to MB/CNS-PNET and 10 due to supposed late effects from the treatment.Survival was comparable to data from other population-based studies. The importance of GTR for survival was corroborated. Reporting real-world data remains crucial to know the true outcome of patients treated outside clinical trials.

OBJECTIVEThe authors present population-based epidemiological data for craniosynostosis regarding incidence, age at diagnosis, sex differences, and frequency of syndromic and familial cases.METHODSThe prospective registry of the Norwegian National Unit for Craniofacial Surgery was used to retrieve data on all individuals with craniosynostosis treated between 2003 and 2017. The cohort was divided into three 5-year groups based on year of birth: 2003–2007, 2008–2012, and 2013–2017.RESULTSThe authors identified 386 individuals with craniosynostosis. Of these, 328 (85%) consented to be registered with further information. The incidence increased significantly during the study period and was 5.5 per 10,000 live births (1/1800) in the last 5-year period. The increase was seen almost exclusively in the nonsyndromic group. Syndromic craniosynostosis accounted for 27% of the cases, and the incidence remained stable throughout the three 5-year periods. Both syndromic and nonsyndromic craniosynostosis were highly suture specific. There was a male preponderance (male/female ratio 2:1), and males accounted for 75% of the individuals with midline synostosis. Overall, 9.5% were index individuals in families with more than one affected member; of these, 73% were nonsyndromic cases.CONCLUSIONSThe incidence of craniosynostosis increased during the study period, and the observed incidence is among the highest reported. The authors attribute this to increasing awareness among healthcare professionals. The number of syndromic cases was high, likely due to a broader definition compared to the majority of earlier reports. The study revealed a high number of familial cases in both syndromic and nonsyndromic craniosynostosis, thus highlighting the importance of genetics as an underlying cause of craniosynostosis.

The purpose of this cross-sectional study was to investigate long-term social attainment in physically well-functioning adult survivors of pediatric brain tumour (PBT) and identify demographic, medical, and psychological factors related to poor social outcomes, with a special focus on the significance of executive dysfunction. One hundred and fourteen PBT survivors and a healthy control group provided personal data on social outcomes, i.e., education, work, and government benefits, and completed questionnaires on executive function (EF), psychological and emotional difficulties, and fatigue. A significantly higher number of survivors compared to healthy controls reported having received educational adjustments and substantial government benefits, and significantly more survivors than controls were currently not engaged in regular employment/training. PBT survivors and healthy controls did not differ on educational level or living situation. The factors most strongly associated with poor social outcomes were self-reported executive dysfunction, difficulties with adaptive functioning, and fatigue. The findings show that physically well-functioning PBT survivors are at risk of poorer social outcomes and financial dependence in adulthood compared to their healthy peers, and underline the importance of investigating EF in short- and long-term follow-ups. Future rehabilitation efforts should focus more on compensatory strategies for executive dysfunction and improving EF skills.

Background Clear identification of tumor subtype is the main predictor of patient outcome and ultimately what is considered an adequate level of surgical risk. At brain tumor resection, imaging modalities and intraoperative histology often give an ambigious diagnosis, complicating intraoperative surgical decision-making. Here, we report a nanopore DNA methylation analysis (NDMA) sequencing approach combined with machine learning for classification of tumor entities that could be used intraoperatively. Methods We analyzed 50 biopsies obtained from biobanked tissue (43, prospective) or sampled at surgery (7, intraoperative) from 20 female and 30 male patients with a median age of 8 years. DNA was extracted using spin columns, quantified on a Qubit fluorometer and assessed for purity using NanoDrop spectrophotometer. DNA was then barcoded with the Rapid Barcoding kit from Oxford Nanopore technologies and loaded onto a MinION flow cell. Sequencing was performed for 3 hours (intraoperative) and 24 hours (prospective). Raw reads were basecalled using the Guppy algorithm, then fed into a snakemake workflow (nanoDx pipeline). This generated a report showing the copy number profile, genome-wide methylation status and subclassification of the tumor according to the Heidelberg reference cohort. Results Twelve different tumor classes were discovered within our cohort spanning from WHO Grade I to Grade IV. The results generated by NDMA were concordant with standard neuropathological diagnosis in 43 out of 50 cases (86%). Of the discordant cases, six were due to the biological complexity of the tumor and one case was misclassified by the pipeline. NDMA enabled correct subclassification of 6/7 intraop cases within a mean of 129 minutes. Conclusion NDMA can accurately subclassify tumor entities intraoperatively and guide surgical procedures when preoperative imaging and frozen section evaluation are unclear.

Objective To characterize shifts from the 1960s to the first decade in the 21st century as to diagnostics, case-mix, and surgical management of pediatric patients undergoing permanent CSF diversion procedures. Methods One hundred and thirty-four patients below 15 years of age were the first time treated with CSF shunt or ETV for hydrocephalus or idiopathic intracranial hypertension (IIH) in 2009–2013. This represents our current practice. Our previously reported cohorts of shunted children 1967–1970 (n = 128) and 1985–1988 (n = 138) served as backgrounds for comparison. Results In the 1960s, ventriculography and head circumference measurements were the main diagnostic tools; ventriculoatrial shunt was the preferred procedure (94 %), neural tube defect (NTD) was the leading etiology (33 %), and overall 2-year survival rate was 76 % (non-tumor survival 84 %). In the 1980s, computerized tomography (CT) was the preferred diagnostic imaging tool; ventriculoperitoneal shunt (VPS) had become standard (91 %), the proportion of NTD children declined to 17 %, and the 2-year survival rate was 91 % (non-tumor survival 95 %). Hydrocephalus caused by intracranial hemorrhage had, on the other hand, increased from 7 to 19 %. In the years 2009–2013, when MRI and endoscopic third ventriculocisternostomy (ETV) were matured technologies, 73 % underwent VPS, and 23 % ETV as their initial surgical procedure. The most prevalent etiology was CNS tumor (31 %). The proportion of NTD patients was yet again halved to 8 %, while intracranial hemorrhage was also reduced to 12 %. In this last period, six children were treated with VPS for Idiopathic Intracranial Hypertension (IIH) due to unsatisfactory response to medical treatment. They all had headache, papilledema, and visual disturbances and responded favorably to treatment. The 2 years of survival was 92 % (non-tumor survival 99 %). In contrast to the previous periods, there was no early shunt related mortality (2 years). Aqueductal stenosis was a small but distinctive group in all cohorts with 5, 6 and 3 % respectively. Conclusions The case-mix in pediatric patients treated with permanent CSF diversion has changed over the last half-century. With the higher proportion of children with CNS tumor patients and inclusion of the IIH children, the median age at initial surgery has shifted substantially from 3.2 to 14 months. Between the 1960s and the current cohort, 2 years of all-cause mortality fell from 24 to 8 %. Prolonged asymptomatic periods, extending 15 years, were relatively common. Nevertheless, 18 patients experienced shunt failure more than 15 years after last revision, and first-time shunt failure has been observed 29 years after initial treatment. This underscores the importance of life-long follow-up.

We have previously identified two ALK rearrangements in a subset of ependymal tumors using a combination of cytogenetic data and RNA sequencing. The aim of this study was to perform an unbiased search for fusion transcripts in our entire series of ependymal tumors. Fusion analysis was performed using the FusionCatcher algorithm on 12 RNA-sequenced ependymal tumors. Candidate transcripts were prioritized based on the software's filtering and manual visualization using the BLAST (Basic Local Alignment Search Tool) and BLAT (BLAST-like alignment tool) tools. Genomic and reverse transcriptase PCR with subsequent Sanger sequencing was used to validate the potential fusions. Fluorescent in situ hybridization (FISH) using locus-specific probes was also performed. A total of 841 candidate chimeric transcripts were identified in the 12 tumors, with an average of 49 unique candidate fusions per tumor. After algorithmic and manual filtering, the final list consisted of 24 potential fusion events. Raw RNA-seq read sequences and PCR validation supports two novel fusion genes: a reciprocal fusion gene involving UQCR10 and C1orf194 in an adult spinal ependymoma and a TSPAN4-CD151 fusion gene in a pediatric infratentorial anaplastic ependymoma. Our previously reported ALK rearrangements and the RELA and YAP1 fusions found in supratentorial ependymomas were until now the only known fusion genes present in ependymal tumors. The chimeric transcripts presented here are the first to be reported in infratentorial or spinal ependymomas. Further studies are required to characterize the genomic rearrangements causing these fusion genes, as well as the frequency and functional importance of the fusions. © 2016 Wiley Periodicals, Inc.

Background: A previous study based on Norwegian Cancer Registry data suggested regional differences in overall survival (OS) after treatment for medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor (CNS-PNET) in Norway. The purpose of the present study was to confirm in an extended cohort whether there were regional differences in outcome or not, and if so try to identify possible explanations. Material and methods: Data from patients aged 0–20 years diagnosed with and treated for MB/CNS-PNET at all four university hospitals in Norway from 1974 to 2013 were collected and compared. Results: Of 266 identified patients, 251 fulfilled inclusion criteria. MB was diagnosed in 200 and CNS-PNET in 51 patients. Five-year OS and event-free survival (EFS) were 59% and 52%, respectively. There was a significant difference in five-year OS and EFS between MB and CNS-PNET patients; 62% versus 47% (P = 0.007) and 57% versus 35% (P < 0.001). In multivariable analysis, two factors were found to significantly contribute to improved five-year OS and EFS, whereas one factor contributed to improved five-year OS only. Gross total resection (GTR) versus non-GTR (hazard ratio [HR] 0.53, P = 0.003; HR 0.46, P < 0.001) and cerebrospinal irradiation (CSI) versus non-CSI (HR 0.24, P < 0.001; HR 0.28, P < 0.001) for both, and treatment outside Oslo University Hospital for OS only (HR 0.64, P = 0.048). Conclusion: Survival was comparable with data from other population-based studies, and the importance of GTR and CSI was confirmed. The cause for regional survival differences could not be identified.

Object The aim of this study is to delineate the long-term results for patients going through surgery for pediatric brain tumors in the first 6 months of life. Methods Thirty consecutive children (1–182 days old) who underwent primary resection for a brain tumor during the years 1973–2012 were included in this retrospective study on surgical morbidity, mortality rate, academic achievement, and/or work participation. Gross motor function and activities of daily life were scored according to the Barthel index. Results Of the 30 patients, 11 children had surgery in the first 3 months of life (1 to 88 days) and 19 were aged 3 to 6 months (94–182 days) at the time of surgery. The male/female ratio was 1.0 (15/15). No patients were lost to follow-up. Two patients died in the postoperative period (30 days). Another eight patients died during the follow-up. Twenty patients are alive, with follow-up times from 2 to 38 years, median 13 years. Among the 28 children who survived the primary resection, eight underwent repeat surgery from 6 months to 5 years after the first operation. Two children were operated three times, and one of these also a fourth time. Gross total resection (GTR) was achieved in 20 of the primary resections, subtotal resection (STR) in 6, and in the last 4, only a biopsy or a partial resection was performed. Nine children received adjuvant chemotherapy and three of these also radiotherapy (in the years 1979–1987). Among the 20 survivors, the Barthel index is normal (100) in 18 patients, 40 in one, and 20 in the last one. Eight tumors were located to the posterior fossa, and 22 were supratentorial. Eighteen tumors were histologically low-grade (WHO grade I–II), most of these were plexus papillomas (7) or astrocytomas (7), and 12 were high-grade (WHO grade III–IV); PNET/medulloblastomas (6), ependymoma (2), glioblastoma (2), teratoma, and plexus carcinoma. Conclusion Infants with brain tumors may clearly benefit from surgical resection with favorable results even for prolonged periods of time. Ten children died, two of them with prolonged survival for 9 and 29 years. Among the 20 survivors, a stable very long-term result appears obtainable in 18 also when it comes to quality of life. Four of the survivors have been treated for highly malignant tumors with a follow-up of 5, 11, 14, and 26 years. One of our infant patients treated for GBM in 1982, lived for 29 years, however, with a progressive decline in the quality of life probably due to postoperative whole-brain radiation.

A 13-year-old boy with severe clinical symptoms and signs underwent surgery for a posterior fossa ependymoma in 1954. The tumor was adjacent to the floor of the fourth ventricle, and surgery was complicated by profound bleeding. Therefore, only a partial resection was performed. Postoperative radiotherapy was given to the posterior fossa. The recovery was uneventful, and he has been in full-time work until the age of 62 years and is now 74 years old. Repeated MRI scans demonstrate a stable residual fourth ventricular tumor.

Ependymomas are rare tumors of the central nervous system (CNS). They are classified based on tumor histology and grade, but the prognostic value of the WHO grading system remains controversial. Treatment is mainly surgical and by radiation. An improved knowledge of ependymoma biology is important to elucidate the pathogenesis, to improve classification schemes, and to identify novel potential treatment targets. Only 113 ependymoma karyotypes with chromosome aberrations are registered in the Mitelman database. We present the first study of ependymoma genomes combining karyotyping and high resolution comparative genomic hybridization (HR-CGH). Nineteen tumor samples were collected from three pediatric and 15 adult patients treated at Oslo University Hospital between 2005 and 2012. Histological diagnoses included subependymoma and myxopapillary ependymoma (WHO grade I), ependymoma (WHO grade II) and anaplastic ependymoma (WHO grade III). Four tumors were intraspinal and 15 were intracranial. Seventeen samples were successfully karyotyped, HR-CGH analysis was undertaken on 17 samples, and 15 of 19 tumors were analyzed using both methods. Twelve tumors had karyotypic abnormalities, mostly gains or losses of whole chromosomes. Structural rearrangements were found in four tumors, in two of which 2p23 was identified as a breakpoint region. Twelve tumors displayed genomic imbalances by HR-CGH analysis with loss of material at 6q as the most common. 6q loss, which was detected by one or both methods in seven of 12 (58%) abnormal tumors, and 5p gain (observed in five tumors; 42%) were the most common genomic aberrations in this series.

Object The objective of this study was to delineate the long-term results of surgical treatment of pediatric low-grade cerebellar astrocytoma. Methods One hundred consecutive children and adolescents (0–19 years old) who underwent primary tumor resection for a low-grade cerebellar astrocytoma during the years 1980–2011 were included in this retrospective study on surgical morbidity, mortality rate, academic achievement, and/or work participation. Gross motor function and activities of daily living were scored according to the Barthel Index. Results Of the 100 patients, 61 children were in the 1st decade, and 39 were 10–19 years old. The male/female ratio was 1.13:1 (53 males, 47 females). No patients were lost to follow-up. There were no deaths in this series and all 100 patients are currently alive. In 29 patients, the follow-up duration was less than 10 years, in 37 it was between 10 and 19 years, and in 34 it was between 20 and 31 years. The Barthel Index was 100 (normal) in 97 patients, 90 in 2 patients, and 40 in the last patient. A total of 113 tumor resections were performed. Two patients underwent further tumor resection due to MRI-confirmed residual tumor demonstrated on the immediate postoperative MR image (obtained the day after the initial procedure). Furthermore, 9 children underwent repeat tumor resection after MRI-confirmed progressive tumor recurrence up to 10 years after the initial operation. Two of these patients also underwent a third resection, without subsequent radiation therapy, and have experienced 8 and 12 years of tumor-free follow-up thereafter, respectively. A total of 15% of the patients required treatment for persistent hydrocephalus. Conclusions Low-grade cerebellar astrocytoma is a surgical disease, in need of long-term follow-up, but with excellent long-term results. Nine percent of the children in this study underwent repeated surgery due to progressive tumor recurrence, and 15% were treated for persistent hydrocephalus.

We describe a patient with a median facial cleft with a frontoethmoidal encephalocele, hypertelorism, hydrocephalus, and cerebrospinal fluid (CSF) leakage referred to our department due to numerous complications after previous surgical treatments. An 8-year-old girl, born with median cleft syndrome, underwent neurosurgical repair of the encephalocele at another hospital and cleft lip/palate repair later in the same year. Her hydrocephalus was treated with a ventriculoperitoneal shunt, but she underwent numerous shunt revisions due to recurrent intracerebral infections. In 2008, she was rehospitalized due to a gram-negative meningitis and cerebral abscess. She underwent surgery where part of her frontal bone was removed due to osteomyelitis. She was referred to our department due to persistent CSF leakage, recurrent infections, and significant dura defect. In addition, she had hypertelorism and a strongly reduced vision. We performed a monobloc and facial bipartition osteotomy where 15 mm of her frontal and nasal bone was removed after facial bipartiton. The dura defect was closed using a free fasciocutanous flap. The patient had no CSF leakage or infections postoperatively, and her hypertelorism was reduced. The case represents the first monobloc and facial bipartition osteotomy performed in Norway as a part of the treatment of median cleft syndrome with a nasoethmoidal encephalocele.

We report on an infant who underwent gross total resection (GTR) of a posterior fossa ependymoblastoma in the second month of life followed by chemotherapy with uneventful long-term survival for 12 years. Postoperative radiotherapy has been considered obligate to have a chance for prolonged survival, but is inadvisable in infants. To our knowledge, this is the first reported long-term survival in an infant treated for ependymoblastoma.

Functional neuroimaging studies consistently report language-related cerebellar activations, but evidence from the clinical literature is less conclusive. Here, we attempt to bridge this gap by testing the effect of focal cerebellar lesions on cerebral activations in a reading task previously shown to involve distinct cerebellar regions. Patients (N = 10) had lesions primarily affecting medial cerebellum, overlapping cerebellar regions activated during the presentation of random word sequences, but distinct from activations related to semantic prediction generation and prediction error processing. In line with this pattern of activation–lesion overlap, patients did not differ from matched healthy controls (N = 10) in predictability-related activations. However, whereas controls showed increased activation in bilateral auditory cortex and parietal operculum when silently reading familiar words relative to viewing letter strings, this effect was absent in the patients. Our results highlight the need for careful lesion mapping and suggest possible roles for the cerebellum in visual-to-auditory mapping and/or inner speech.

Spinal dysraphism is a group of congenital anomalies of the spine characterized by a midline defect affecting the nervous tissue and its bony and soft tissue coverings. Closed spinal dysraphism, spina bifida occulta, refers to skin-covered lesions. However, there are a number of cutaneous stigmata or other physical signs that serve as indicators of an underlying dysraphic malformation of the lower spinal canal.Based upon relevant literature, we present a review of occult spina bifida.The cutaneous stigmata that may indicate an underlying dysraphism are particularly hairy patches, subcutaneous lipomas, capillary hemangiomas, dorsal dermal sinuses and sacral cutaneous pits. The clinical examination of a child with lumbosacral cutaneous stigmata should focus on neurological signs and symptoms, urological disturbances and orthopaedic deformities in the lower limbs. Spinal MRI is the imaging modality of choice in children presenting with features consistent with occult spinal dysraphism. Children with occult spinal dysraphism should be referred to a neurosurgical unit.

The relationships among ischaemic GABA efflux from brain tissue and extracellular and intracellular concentrations of sodium, chloride and potassium ions were investigated by means of 1) transverse hippocampal slices from rat and 2) functional expression of a high affinity GABA transporter in Xenopus oocytes. Brain slices were incubated for 20 min in medium where extracellular sodium and chloride were substituted with impermeant ions. Isethionate (Iseth) substitution for chloride generated a 7-fold increase in GABA efflux. Choline (Chol) but not N-methyl-D-glucamine (NMDG) substitution for sodium likewise increased GABA efflux. Reducing the osmolarity of the medium by decreasing both sodium and chloride concentrations (Hyp) increased GABA efflux 3-fold. This release was blocked by mannitol (Man). Blocking sodium channels with 1 microM of tetrodotoxin (TTX) also increased the release 3-fold. Energy deprivation (ED) increased the GABA release 50-fold. ED/Iseth left the release unchanged, ED/Chol increased the GABA efflux by 23%, whereas ED/NMDG reduced the release by 41%. Adding mannitol did not block the ED-evoked release, whereas TTX reduced it by 52%. Release of preloaded [3H]-GABA from oocytes expressing the GAT-1 GABA transporter was then examined. Depolarisation by current injection or 100 mM extracellular K+ did not increase GABA release. Sodium chloride injection, however, caused membrane depolarisation and a 100-fold increased GABA efflux from the oocytes. This release was blocked when the osmolarity was increased extracellularly by adding mannitol. These results show that 1) TTX releases GABA from brain tissue but blocks release during ED, 2) the high affinity GABA carrier must be altered in order to reverse, 3) ischaemic GABA release is sodium independent, and is modulated by large cations, 4) mannitol blocks the reversal of high affinity carriers in oocytes, but the release from brain slices during ED is unaffected. Taken together, the results suggest that ischaemic release of GABA from brain tissue does not occur by means of reversed high affinity carriers alone, but rather that it is controlled by more complex mechanisms.

Methods Ten consecutive children (0–18 years) who underwent primary tumor resection for a spinal ependymoma between 1980 and 2011 were included in this retrospective study. Gross motor function and activities of daily life were scored according to the Barthel Index. Conclusion Three out of six pediatric patients treated for spinal myxopapillary ependymoma are disease-free after 11 to 33 years of follow-up. The other three have progressive disease, after relapses occurring after 4.5, 7, and 20 years, respectively. One out of two patients with grade II ependymoma had progressive disease from 10 years after initial surgery but is in full-time work in spite of widespread metastatic disease after 32 years. One of the two children with grade III tumor died from progressive disease 17 years from primary diagnosis, while the last one is tumor-free after 19 years. The quality of life is good for three of the four patients with widespread disease, and they are managed conservatively aiming at symptomatic treatment intervention if necessary. We strongly advocate lifelong follow-up for children treated for spinal ependymomas.